Transferrin-Conjugated Nanostructured Lipid Carriers for Targeting Artemisone to Melanoma Cells.

We report a successful formulation of Artemisone (ATM) in transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs), achieving nearly a five-times increase in cell toxicity. The escalating cost of new drug discoveries led to the repurposing of approved drugs for new indications. This study incorporated Artemisone, an antimalarial drug, into a nanostructured lipid carrier (NLC) and tested for possible anticancer effects. The aim was to develop NLCs, and transferrin-conjugated NLCs (NLC-Tf) encapsulating Artemisone to enhance its delivery and anticancer activity. NLC formulations were prepared using high-pressure homogenization followed by ultrasonication and were characterized by particle size, zeta potential, and PDI. The conjugation of (Tf) to (NLC) was confirmed using IR, and the anticancer activity was tested using MTS assay. All formulations were in the nanometer size range (140-167 nm) with different zeta potential values. IR spectroscopy confirmed the successful conjugation of transferrin to NLC. Upon testing the formulations on melanoma cell lines using MTS assay, there was a significant decrease in viability and an increase in the encapsulated ATM-Tf toxicity compared to positive control ATM. The NLCs presented a promising potential carrier for delivering ATM to melanoma cells, and further conjugation with Tf significantly improved the ATM cytotoxicity.

Quercetin-Loaded Nanostructured Lipid Carrier In Situ Gel for Brain Targeting Through Intranasal Route: Formulation, In Vivo Pharmacokinetic and Pharmacodynamic Studies.

Quercetin (QT) shows potential for protecting against neurodegenerative diseases like Alzheimer's. However, its limited bioavailability and instability in physiological pH hinder its clinical use. The purpose of this work is to construct QT-filled nanostructured lipid carriers (QT-NLC) intranasal in situ gel to enhance pharmacokinetic and pharmacodynamic performance. NLCs were developed using a melt emulsification-high-pressure homogenization and were optimized using design expert software with the Box-Behnken design. NLCs were then incorporated into an in situ gel based on Lutrol F127 and further characterized. The pharmacodynamics of the formulation was evaluated in neurodegeneration induced by trimethyl tin (TMT) Wistar rats. The optimized QT in situ gel had spherical shape, entrapment efficiency of 96.1 ± 4.40%, and in vitro drug release of 83.74 ± 1.40%. The mean particle size was 123.3 ± 5.46 nm. After intranasal administration, in vivo single-dose pharmacokinetic studies demonstrated a significant therapeutic concentration of drug in CNS, having Cmax 183.41 ± 11.76 ng/mL and Tmax of 2 h. The more brain targeting efficiency of NLCs was proved by the developed QT in situ gel, which had a higher drug targeting efficiency (DTE) of 117.47% and drug targeting potential (DTP) of 88.9%. As compared to the neurodegeneration control group, the QT in situ gel-treated group had significantly decreased escape latency and pathlength. Biochemical analysis and histological investigations demonstrated that QT in situ gel exhibited superior anti-Alzheimer's potential compared to standard drug, donepezil. The promising results of the developed and optimized intranasal QT in situ gel suggest its potential and can be used in Alzheimer's disease management.

Assessment of anti-arthritic activity of lipid matrix encased berberine in rheumatic animal model.

The purpose of this study was to evaluate the drug delivery and therapeutic potential of berberine (Br) loaded nanoformulation in rheumatoid arthritis (RA)-induced animal model. The Br-loaded NLCs (nanostructured lipid carriers) were prepared employing melt-emulsification process, and optimised through Box-Behnken design. The prepared NLCs were assessed for in-vitro and in-vivo evaluations. The optimised NLCs exhibited a mean diameter of 180.2 ± 0.31 nm with 88.32 ± 2.43% entrapment efficiency. An enhanced anti-arthritic activity with reduced arthritic scores to 0.66 ± 0.51, reduction in ankle diameter to 5.80 ± 0.27 mm, decline in paw withdrawal timing, and improvements in walking behaviour were observed in the Br-NLCs treated group. The radiographic images revealed a reduction in bone and cartilage deformation. The Br-NLCs showed promising results in the management of RA disease, can be developed as an efficient delivery system at commercial levels, and may be explored for clinical application after suitable experiments in the future.

Development of Computational In Silico Model for Nano Lipid Carrier Formulation of Curcumin.

The oral delivery system is very important and plays a significant role in increasing the solubility of drugs, which eventually will increase their absorption by the digestive system and enhance the drug bioactivity. This study was conducted to synthesize a novel curcumin nano lipid carrier (NLC) and use it as a drug carrier with the help of computational molecular docking to investigate its solubility in different solid and liquid lipids to choose the optimum lipids candidate for the NLCs formulation and avoid the ordinary methods that consume more time, materials, cost, and efforts during laboratory experiments. The antiviral activity of the formed curcumin-NLC against SARS-CoV-2 (COVID-19) was assessed through a molecular docking study of curcumin's affinity towards the host cell receptors. The novel curcumin drug carrier was synthesized as NLC using a hot and high-pressure homogenization method. Twenty different compositions of the drug carrier (curcumin nano lipid) were synthesized and characterized using different physicochemical techniques such as UV-Vis, FTIR, DSC, XRD, particle size, the zeta potential, and AFM. The in vitro and ex vivo studies were also conducted to test the solubility and the permeability of the 20 curcumin-NLC formulations. The NLC as a drug carrier shows an enormous enhancement in the solubility and permeability of the drug.

Novel Strategies against Cancer: Dexibuprofen-Loaded Nanostructured Lipid Carriers.

The aim of this work was to design innovative nanostructured lipid carriers (NLCs) for the delivery of dexibuprofen (DXI) as an antiproliferative therapy against tumoral processes, and overcome its side effects. DXI-NLC samples were prepared with beeswax, Miglyol 812 and Tween 80 using high-pressure homogenization. A two-level factorial design 24 was applied to optimize the formulation, and physicochemical properties such as particle size, zeta potential, polydispersity index and entrapment efficiency were measured. Optimized parameters of DXI-NLCs exhibited a mean particle size of 152.3 nm, a polydispersity index below 0.2, and high DXI entrapment efficiency (higher than 99%). Moreover, DXI-NLCs provided a prolonged drug release, slower than the free DXI. DXI-NLCs were stable for 2 months and their morphology revealed that they possess a spherical shape. In vitro cytotoxicity and anticancer potential studies were performed towards prostate (PC-3) and breast (MDA-MB-468) cancer cell lines. The highest activity of DXI-NLCs was observed towards breast cancer cells, which were effectively inhibited at 3.4 µM. Therefore, DXI-NLCs constitute a promising antiproliferative therapy that has proven to be especially effective against breast cancer.

Design of Quercetin-Loaded Natural Oil-Based Nanostructured Lipid Carriers for the Treatment of Bacterial Skin Infections.

The biological activity of natural plant-oil-based nanostructured lipid carriers (NPO-NLCs) can be enhanced by the encapsulation of bioactive compounds, and they in turn can improve topical delivery of the drugs. Quercetin (QR), a vital plant flavonoid, expresses antibacterial properties, and we recently showed that empty NPO-NLCs also have antimicrobial activity. The main objective of this study was to evaluate the synergetic effect of loading natural plant-oil-based nanostructured lipid carriers with quercetin (QR-NPO-NLCs) as a topical delivery system for the treatment of bacterial skin infections. Five nanostructured lipid carrier systems containing different oils (sunflower, olive, corn, coconut, and castor) were engineered. The particles' stability, structural properties, bioavailability, and antimicrobial activity were studied. NLCs with an average size of <200 nm and Z-potential of −40 mV were developed. Stable QR-NPO-NLCs were obtained with high encapsulation efficiency (>99%). The encapsulation of QR decreased cytotoxicity and increased the antioxidant effect of nanocarriers. An increase in antibacterial activity of the systems containing QR was demonstrated against Staphylococcus aureus. QR-NPO-NLCs could transport QR to an intranuclear location within HaCaT cells, indicating that QR-NPO-NLCs are promising candidates for controlled topical drug delivery.

Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet.

Ezetimibe (EZE) possesses low aqueous solubility and poor bioavailability and in addition, its extensive hepatic metabolism supports the notion of developing a novel carrier system for EZE. Ezetimibe was encapsulated into nanostructured lipid carriers (EZE-NLCs) via a high pressure homogenization technique (HPH). A three factor, two level (23) full factorial design was employed to study the effect of amount of poloxamer 188 (X1), pressure of HPH (X2) and number of HPH cycle (X3) on dependent variables. Particle size, polydispersity index (PDI), % entrapment efficiency (%EE), zeta potential, drug content and in-vitro drug release were evaluated. The optimized formulation displays pragmatic inferences associated with particle size of 134.5 nm; polydispersity index (PDI) of 0.244 ± 0.03; zeta potential of -28.1 ± 0.3 mV; % EE of 91.32 ± 1.8% and % CDR at 24-h of 97.11%. No interaction was observed after X-ray diffraction (XRD) and differential scanning calorimetry (DSC) studies. EZE-NLCs (6 mg/kg/day p.o.) were evaluated in the high fat diet fed rats induced hyperlipidemia in comparison with EZE (10 mg/kg/day p.o.). Triglyceride, HDL-c, LDL-c and cholesterol were significantly normalized and histopathological evaluation showed normal structure and architecture of the hepatocytes. The results demonstrated the superiority of EZE-NLCs in regard to bioavailability enhancement, dose reduction and dose-dependent side effects.

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity, and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography.

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, -38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1ß, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.

Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies.

NLCs have provoked the incessant impulsion for the development of safe and valuable drug delivery systems owing to their exceptional physicochemical and then biocompatible characteristics. Throughout the earlier period, a lot of studies recounting NLCs based formulations have been noticeably increased. They are binary system which contains both solid and liquid lipids aiming to produce less ordered lipidic core. Their constituents particularly influence the physicochemical properties and effectiveness of the final product. NLCs can be fabricated by different techniques which are classified according to consumed energy. More utilization NLCs is essential due to overcome barriers surrounded by the technological procedure of lipid-based nanocarriers' formulation and increased information of the core mechanisms of their transport via various routes of administration. They can be used in different applications and by different routes such as oral, cutaneous, ocular and pulmonary. This review article seeks to present an overview on the existing situation of the art of NLCs for future clinics through exposition of their applications which shall foster their lucid use. The reported records evidently demonstrate the promise of NLCs for innovate therapeutic applications in the future.

CT and MR imaging findings of solitary nevus lipomatosus cutaneous superficialis: radiological-pathological correlation.

OBJECTIVE: This study assessed the CT and MRI findings of solitary nevus lipomatosus cutaneous superficialis (NLCS). MATERIALS AND METHODS: Eleven patients with histopathologically and clinically confirmed solitary NLCS who underwent CT and/or MRI were enrolled. Radiological and histopathological findings of elevated lesions located above the level of the surrounding normal skin surface and coexisting subcutaneous lipoma-like lesions were assessed retrospectively. RESULTS: Elevated skin lesions were observed in all 11 patients; these lesions were pedunculated in 4 patients (36%) and broad-based in 7 (64%). The CT attenuation of elevated lesions was fat attenuation in 2 out of 7 patients (29%), slightly increased fat attenuation in 4 out of 7 (57%), and combined fat and soft-tissue attenuation in 1 out of 7 (14%). The MR signal intensity of elevated lesions on T1-weighted images was fat signal intensity in 2 out of 6 patients (33%), slightly decreased fat signal intensity in 3 out of 6 (50%), and combined fat signal intensity and hypointensity in 1 out of 6 (17%). Subcutaneous lipoma-like lesions with fat attenuation and/or fat signal intensity were observed in 6 out of 11 patients (55%). Histopathologically, various amounts of fatty tissue and collagenous fiber were observed within the elevated lesions in all 11 patients. CONCLUSION: The CT and MRI features of solitary NLCS were the broad-based or pedunculated elevated lesions, including fatty components. Additionally, subcutaneous lipoma-like lesions were frequently observed.

Squinted Airborne Synthetic Aperture Radar Imaging with Unknown Curved Trajectory.

The imagery of airborne highly squinted synthetic aperture radar (SAR) with curved trajectory is a challenging task due to the translational-variant range cell migration (RCM) and azimuth modulation. However, in most cases of practical application, the curved trajectory cannot be accurately known, which brings greater difficulties to the imaging problem. To accommodate these issues, we propose a novel motion modelling and optimisation based imaging algorithm for the highly squinted SAR with unknown curved trajectory. First, to correct the translational-variant RCM, a coarse-to-fine RCM correction scheme as well as a range perturbation approach is applied. Afterwards, an optimisation model of motion information under the criterion of minimum entropy is built during the azimuth processing by nonlinear chirp scaling (NLCS). Correspondingly, a differential evolution (DE) optimisation strategy is proposed to estimate the motion information in an iterative manner. We empirically compare the proposed algorithms with several state-of-the-art highly squinted curved SAR imaging algorithms. Numerical results show the effectiveness of the proposed method in the case without any prior information of the curved trajectory.

Systematic development and characterization of curcumin-loaded nanogel for topical application.

Curcumin (CUR) conventional formulation has poor oral bioavailability due to low solubility and low stability. Also, it extensively undergoes first-pass-metabolism showing low biological activity. The present work focuses on the systematic development and characterization of CUR-loaded Nanostructured Lipid Carrier (CUR-NLCs) having promising topical applications for skin diseases such as psoriasis. CUR-NLCs were prepared by using high-speed homogenization method. Quality by design approach was exploited to select out Critical Process Parameters i.e. homogenization speed (X1), homogenization time (X2), amount of lipid (X3), solid lipids (SL): liquid lipids (LL) (X4), and surfactant conc. (X5) using Plackett-Burman design and for obtaining critical quality attributes i.e. particle size (Y1) and entrapment efficiency (Y2) using Box-Behnken design. The developed NLCs were found to be nano-metric in size (189.4 ± 2.6 nm) with a low polydispersity index (0.262 ± 0.24), zeta potential (-21.45 ± 1.3 mV), and showed good encapsulation efficiency (86.72 ± 09%). Surface morphology determined by SEM and AFM revealed the spherical shape of the NLCs with a smooth surface. XRD studies showed NLCs in the amorphous state. After incorporation of NLCs into a nanogel, it was characterized for pH, rheological behavior, spreadability, in vitro occlusion, and in vitro release kinetics. The drug release from NLC in 24 h was found to be 60.2 ± 0.45% indicating a sustained release pattern. Ex vivo permeation studies revealed a good permeation flux (0.453 ± 0.76 µg/cm2.h) and retention (60.2 ± 0.45%) of CUR in the skin epidermis. Thus, developed CUR-NLCs can be a potential delivery system and a promising therapeutic approach for the effective treatment of psoriasis.

Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: preformulation screening studies and statistical hybrid-design for optimization of variables.

The objective of the present project was to develop and optimize the Ibuprofen (IBU)-loaded nanostructured lipid carrier (IBU-NLCs) for sustained-release ocular drug delivery using a quality-by-design (QbD) approach. The BCS class II drug IBU was selected as the model drug for the preparation of IBU-NLCs by melt-emulsification and ultrasonication technique. Extensive preformulation screening of the components of NLC dispersion (i.e. solid and liquid lipid, surfactants, and osmolality agents) was performed. From the various lipids screened, Dynasan®114 and Miglyol®840 were selected as the most suitable solid and liquid lipid, respectively. These lipids, at a matrix ratio of 6:4, demonstrated a lower melting-point and crystallinity-index based on DSC, XRD, and compatibility studies. Various surfactants were evaluated, and among them, Kolliphor®HS15 demonstrated lower z-average particle size (PS) and polydispersity index (PDI), while Kolliphor®P188 resulted in a zeta potential (ZP) <-20 mV. Glycerol was selected from various osmolality agents due to its negligible effects on physicochemical properties of the optimized formulation. A Plackett-Burman design (PBD) was used for the initial screening of the critical variables, followed by a Box-Behnken design (BBD) for further optimization of the NLC dispersion. The optimized formulation demonstrated the PS of 147 nm, with narrow PDI (0.159), ZP of -25.7 mV, and an entrapment efficiency (EE) of 97.89%. In vitro diffusion of IBU from the optimized IBU-NLC dispersion showed a sustained-release of ∼51% for up to 12 h. Preformulation studies and a statistical hybrid-design approach was effectively applied to incorporate IBU in NLCs, resulting in a robust ophthalmic formulation with superior physicochemical properties.

Ellagic Acid Containing Nanostructured Lipid Carriers for Topical Application: A Preliminary Study.

Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit its use. The aim of the present study was to develop lipid-based nanoparticle formulations able to encapsulate EA for dermal delivery. The EA-loaded nanoparticles were prepared using two different lipid compositions, namely tristearin/tricaprylin (NLC-EA1) and tristearin/labrasol (NLC-EA2). The influence of formulations on size, entrapment efficiency, and stability of EA-loaded nanoparticles was investigated. Cryo-TEM and small-angle X-ray scattering (SAXS) analyses showed that no morphological differences are evident among all the types of loaded and unloaded nanostructured lipid carriers (NLCs). The macroscopic aspect of both NLC-EA1 and NLC-EA2 did not change with time. No difference in size was appreciable between empty and drug-containing NLC, thus the nanoparticle diameter was not affected by the presence of EA and in general no variations of the diameters occurred during this time. The entrapment efficiency of both EA-loaded nanoparticles was almost quantitative. In addition, NLC-EA1 maintained EA stability for almost two months, while NLC-EA2 up to 40 days. FRAP (Ferric reducing ability of plasma) assay showed an antioxidant activity around 60% for both the loaded NLC, as compared to the solution. Although both types of NLC are characterized by some toxicity on HaCaT cells, NLC-EA1 are less cytotoxic than NLC-EA2. Taken together these results demonstrated that the inclusion of EA within NLC could improve the water solubility, allowing for a reduction of the dosage. Moreover, both types of NLC-EA maintained a high antioxidant effect and low toxicity.

Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting.

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600 nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60-85% of drug was slowly released from lipid nanoparticles within 72 h. CPA-NLC with average diameter of 600 nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300 nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300 nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300 nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.

Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects.

Cancer remains the topmost disorders of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.

Adherence to the Mediterranean diet and risk of lung cancer in the Netherlands Cohort Study.

The evidence on a cancer-protective effect of the Mediterranean diet (MD) is still limited. Therefore, we investigated the association between MD adherence and lung cancer risk. Data were used from 120 852 participants of the Netherlands Cohort Study (NLCS), aged 55-69 years. Dietary habits were assessed at baseline (1986) using a validated FFQ and alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol, were calculated. After 20·3 years of follow-up, 2861 lung cancer cases and 3720 subcohort members (case-cohort design) could be included in multivariable Cox regression analyses. High (6-8) v. low (0-3) aMED excluding alcohol was associated with non-significantly reduced lung cancer risks in men and women with hazard ratios of 0·91 (95 % CI 0·72, 1·15) and 0·73 (95 % CI 0·49, 1·09), respectively. aMED-containing models generally fitted better than mMED-containing models. In never smokers, a borderline significant decreasing trend in lung cancer risk was observed with increasing aMED excluding alcohol. Analyses stratified by the histological lung cancer subtypes did not identify subtypes with a particularly strong inverse relation with MD adherence. Generally, the performance of aMED and World Cancer Research Fund/American Institute for Cancer Research dietary score variants without alcohol was comparable. In conclusion, MD adherence was non-significantly inversely associated with lung cancer risk in the NLCS. Future studies should focus on differences in associations across the sexes and histological subtypes. Furthermore, exclusion of alcohol from MD scores should be investigated more extensively, primarily with respect to a potential role of the MD in cancer prevention.

Docetaxel-loaded nanostructured lipid carriers functionalized with trastuzumab (Herceptin) for HER2-positive breast cancer cells.

The aim of the present study was to prepare Herceptin targeted nanostructured lipid carriers (NLCs) of docetaxel (DTX). Herceptin was conjugated by chemical and physical methods to NLCs prepared by solvent extraction technique followed by probe sonication. Different types of fatty amines were used in construction of NLCs. The NLCs were characterized for their antibody coupling efficiency, particle size, zeta potential, polydispersity index, drug entrapment efficiency and drug release profiles. The toxicity of NLCs on MDA-MB-468 (HER2 negative receptor) and BT-474 (HER2 positive) breast cancer cell lines was evaluated by MTT assay. Also their cellular uptake was studied by flow-cytometry and fluorescent microscopy. The results showed the NLCs containing stearyl amine had the lowest particle size, the highest zeta potential and antibody coupling efficiency values. Herceptin binding to NLCs led to reduction in zeta potential and drug entrapment efficiency while, particle size increased. The NLCs containing spermine(SP) released DTX slower than other fatty amines. Non-conjugated nanoparticles containing DTX had more toxicity than the free DTX on both cell lines. Herceptin targeted NLCs caused more mortality on BT-474 cells than MDA-MB-468 cells. Flow-cytometry studies revealed enhanced cellular uptake of nanoparticles chemically conjugated by Herceptin on the BT-474 cells. DTX loaded in chemically conjugated NLCs to Herceptin showed more cytotoxic effects than the physically coated nanoparticles. The Herceptin conjugated NLCs seem promising in oriented delivery of DTX to HER2 positive breast cancer cells.

Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design.

The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X1), soybean oil (X2), and Tween 80 (X3) were used as solid lipid, liquid lipid, and stabilizer, respectively. The particle size of TA-loaded NLCs was lower than 200 nm and the zeta potential displayed the negative charge in all formulations. The percentage encapsulation efficiency (%EE) of the TA-loaded NLCs showed that it was higher than 80% for all formulations. Field emission scanning electron microscope (FESEM) confirmed that the size of TA-loaded NLCs was approximately 100 nm and energy-dispersive X-ray spectroscopy (EDS) confirmed that the TA could be incorporated in the NLC system. The Higuchi model gave the highest value of the R², indicating that this model was a fit for the TA release profiles of TA-loaded NLCs. Confocal laser scanning microscopy (CLSM) was used to observe the drug penetration within the porcine buccal mucosa and Nile red-loaded NLCs showed significantly higher penetration depth at 8 h than at 2 h. Therefore, TA-loaded NLCs could be an efficient carrier for drug delivery through the buccal mucosa.

Stability of astaxanthin-loaded nanostructured lipid carriers in beverage systems.

BACKGROUND: Nanostructured lipid carriers (NLCs) offer many potential benefits for incorporating lipophilic molecules into clear to opaque food systems. This study examined the stability of astaxanthin-loaded NLCs (Ax-NLCs) in model (solutions with 0 or 12% sucrose; pH 3, 7), semi-actual (whey) and actual (non-alcoholic beer) beverages during 30-60 days storage at 6 or 20 °C. RESULTS: Ax-NLCs (Z-average size: 94 nm), containing α-tocopherol and EDTA as antioxidants, were stabilised with Tween 80 and lecithin, and mixed with the aforementioned beverages at the volume ratio of 3:97. The presence of sucrose, improved the physical stability of Ax-NLCs in acidic model beverage. No astaxanthin loss and particle size growth were observed for Ax-NLCs-added whey. Carbonation and/or thermal pasteurisation of NLCs-added beer led to a major increase in its particles size and astaxanthin loss. Stability of Ax-NLCs in non-pasteurised CO2 -free beer improved at low storage temperature. The organoleptic quality of NLCs-added beers was still acceptable. CONCLUSION: These results indicate that NLCs containing hydrophobic nutraceuticals have potential to be used for functional beverages/foods development. © 2017 Society of Chemical Industry.